Prenatal immune challenge in rats increases susceptibility to seizure-induced brain injury in adulthood

• Prenatal LPS exposure enhanced adult seizure sensitivity to lithium-pilocarpine (LiPC).
• Prenatal LPS exposure enhanced LiPC-induced neuronal injury.
• Prenatal LPS exposure led to decreased explorative activity after LiPC-induced seizures.
• Prenatal LPS exposure exacerbated LiPC-induced spatial learning impairment.

Maternal infection during pregnancy is associated with an increased risk of neurodevelopmental injury. Our aim was to investigate whether prenatal immune challenge could alter susceptibility to seizure-induced brain injury in adulthood. Pregnant Wistar rats were injected intraperitoneally with lipopolysaccharide (LPS) or normal saline (NS) at days 15 and 16 of gestation. At postnatal day 45, seizure susceptibility was assessed in response to lithium-pilocarpine (LiPC) in adult offspring. Four groups were studied, including normal control (NS‐NS), prenatal inflammation (LPS‐NS), adult seizure (NS‐LiPC), and “two-hit” (LPS‐LiPC) groups. Our results demonstrated that adult rat offspring of LPS-exposed dams showed significantly greater susceptibility to LiPC-induced seizures, as well as enhanced hippocampal neuronal injury after seizures. Furthermore, animals in the “two-hit” group performed significantly worse than those from the NS‐LiPC group in the open field test and Morris water maze. Our findings suggest that prenatal immune activation can cause a long-lasting increase in seizure susceptibility and predispose the brain to the damaging effect of seizures later in life.